Nimenrix, INN-meningococcal group A, C, W-135 and Y ...€¦ · Business Park, Clondalkin, Dublin 22, Ireland) as an 16/01/2020 SmPC, Labelling and PL ; Nimenrix EMA/CHMP/652267/2020

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands

An agency of the European Union Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us

Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000

Nimenrix Procedural steps taken and scientific information after the authorisation

Application

number

Scope Opinion/

Notification1

issued on

Commission

Decision

Issued2 /

amended

on

Product

Information

affected3

Summary

PSUSA/10044

/202004

Periodic Safety Update EU Single assessment -

meningococcal group a, c, w135, y conjugate

vaccines (conjugated to tetanus toxoid carrier

protein)

10/12/2020 18/02/2021 SmPC and PL Refer to Scientific conclusions and grounds recommending

the variation to terms of the Marketing Authorisation(s)’ for

PSUSA/10044/202004.

II/0105 To update section 5.1 Pharmacodynamic properties

of the SmPC with information regarding the

effectiveness of Nimenrix, to include real-world data

11/02/2021 SmPC and PL SmPC new text (Section 5.1)

Impact of a single dose of Nimenrix.

1 Notifications are issued for type I variations and Article 61(3) notifications (unless part of a group including a type II variation or extension application or a worksharing application). Opinions are issued for all other procedures. 2 A Commission decision (CD) is issued for procedures that affect the terms of the marketing authorisation (e.g. summary of product characteristics, annex II, labelling, package leaflet). The CD is issued within two months of the opinion for variations falling under the scope of Article 23.1a(a) of Regulation (EU) No. 712/2012, or within one year for other procedures. 3 SmPC (Summary of Product Characteristics), Annex II, Labelling, PL (Package Leaflet).

http://www.ema.europa.eu/how-to-find-ushttp://www.ema.europa.eu/contact

Nimenrix

EMA/176236/2021 Page 2/39

from the Netherlands describing the impact of a

single dose of Nimenrix on the prevention of

meningococcal disease. In addition, a cross-

reference to section 4.2 Posology and method of

administration of the SmPC was included, to direct

the physicians attention to the robust persistence

and booster data in section 5.1 and information in

section 4.4 Special warnings and precautions for use.

In addition, the MAH took the opportunity to include

minor editorial changes to the SmPC and to bring the

Product information in line with the latest QRD

update.

C.I.4 - Change(s) in the SPC, Labelling or PL due to

new quality, preclinical, clinical or pharmacovigilance

data

In 2018, the Netherlands added Nimenrix to the national

immunisation programme as a single dose for toddlers at

14 months of age to replace the meningococcal C conjugate

vaccine. A catch-up campaign with a single dose of

Nimenrix for adolescents 14-18 years of age also initiated

in 2018, and it became routine in 2020 leading to a toddler

and adolescent national immunisation programme. Within

two years, the incidence of meningococcal disease caused

by groups C, W, and Y was significantly reduced by 100%

(95% CI: 14, 100) in individuals 14-18 years of age, 85%

(95% CI: 32, 97) in all vaccine eligible ages (direct effect),

and 50% (95% CI: 28, 65) in non-vaccine eligible ages

(indirect effect). The impact of Nimenrix was primarily

driven by a reduction in group W disease.

For more information, please refer to the Summary of

Product Characteristics.

IA/0106 B.I.b.2.a - Change in test procedure for AS or

starting material/reagent/intermediate - Minor

changes to an approved test procedure

21/12/2020 n/a

IB/0104 C.I.z - Changes (Safety/Efficacy) of Human and

Veterinary Medicinal Products - Other variation

03/11/2020 18/02/2021 SmPC and PL

IB/0103 B.I.a.1.k - Change in the manufacturer of AS or of a

starting material/reagent/intermediate for AS - New

storage site of MCB and/or WCB

09/10/2020 n/a

II/0099/G This was an application for a group of variations.

A.7 - Administrative change - Deletion of

23/07/2020 18/02/2021 Annex II

Nimenrix

EMA/176236/2021 Page 3/39

manufacturing sites

B.I.a.1.e - Change in the manufacturer of AS or of a

starting material/reagent/intermediate for AS - The

change relates to a biological AS or a starting

material [-] used in the manufacture of a

biological/immunological product





















B.I.a.1.j - Change in the manufacturer of AS or of a

starting material/reagent/intermediate for AS -

Replacement or addition of a site where batch

control/testing takes place and any of the test

method at the site is a biol/immunol method


Nimenrix

EMA/176236/2021 Page 4/39

























B.I.a.2.a - Changes in the manufacturing process of

the AS - Minor change in the manufacturing process

of the AS

B.I.b.1.c - Change in the specification parameters

and/or limits of an AS, starting

material/intermediate/reagent - Addition of a new

specification parameter to the specification with its

corresponding test method

Nimenrix

EMA/176236/2021 Page 5/39






B.I.b.1.e - Change in the specification parameters


material/intermediate/reagent - Deletion of a

specification parameter which may have a significant

effect on the overall quality of the AS and/or the FP

B.I.b.2.e - Change in test procedure for AS or

starting material/reagent/intermediate - Other

changes to a test procedure (including replacement

or addition) for the AS or a starting

material/intermediate

B.I.c.1.b - Change in immediate packaging of the AS

- Qualitative and/or quantitative composition for

sterile and non-frozen biological/immunological ASs

B.I.c.1.z - Change in immediate packaging of the AS

- Other variation

B.I.a.1.z - Change in the manufacturer of AS or of a

starting material/reagent/intermediate for AS - Other

variation



variation



variation



variation

Nimenrix

EMA/176236/2021 Page 6/39



variation

II/0098 B.II.d.2.c - Change in test procedure for the finished

product - Substantial change to or replacement of a

biol/immunol/immunochemical test method or a

method using a biol. reagent or replacement of a

biol. reference preparation not covered by an

approved protocol

09/07/2020 n/a

IB/0100 B.I.z - Quality change - Active substance - Other

variation

29/06/2020 n/a

IA/0101 B.III.2.b - Change to comply with Ph. Eur. or with a

national pharmacopoeia of a Member State - Change

to comply with an update of the relevant monograph

of the Ph. Eur. or national pharmacopoeia of a

Member State

18/06/2020 n/a

II/0096 C.I.4 - Change(s) in the SPC, Labelling or PL due to


data

30/01/2020 18/02/2021 SmPC and PL


Grouping of variations to support the introduction of

Pfizer Ireland Pharmaceuticals (Grange Castle

Business Park, Clondalkin, Dublin 22, Ireland) as an

alternative manufacturing and quality control testing

site for the MenAAH-TT, MenCAH-TT, MenW-TT and

MenY-TT Drug Substances.

16/01/2020 18/02/2021 SmPC,

Labelling and

PL

Nimenrix

EMA/176236/2021 Page 7/39

Grouping of variations to support the registration of

a new vial/vial presentation (EU/1/12/767/008) to

replace the existing vial/ampoule presentations. As a

consequence of the introduction of the new vial/vial

presentation, the vial/ampoule presentations

(EU/1/12/767/005-006-007) are being withdrawn.

Hence, the 0.9% NaCl Diluent in ampoules (primary

packaging container) as currently manufactured at

Delpharm Belgium is withdrawn, as well as the

associated secondary packaging site (CRNA Belgium)

used for the related pack-size. This grouping of

variations supports the introduction of Pfizer Puurs

Belgium as a manufacturing and quality control site

for the 0.9% NaCl Diluent in vials used for

MenACWY-TT Drug Product reconstitution for the

new vial/vial presentation. In addition, release

specifications have been updated to align with

compendial requirements.

Product Information (PI) revisions in line with the

above changes affect Annex I, IIIA and IIIB, as well

as Annex A (All Authorised Presentations). In

addition, the MAH took the opportunity to align

SmPC section 4.4 and Annex II with the latest QRD

requirement.


manufacturing sites

B.II.b.1.f - Replacement or addition of a

manufacturing site for part or all of the

manufacturing process of the FP - Site where any

Nimenrix

EMA/176236/2021 Page 8/39

manufacturing operation(s) take place, except batch

release, batch control, and secondary packaging, for

sterile medicinal products (including those that are

aseptically manufactured) excluding biological/

immunological medicinal products

B.II.b.2.a - Change to importer, batch release

arrangements and quality control testing of the FP -

Replacement/addition of a site where batch

control/testing takes place

B.II.d.1.z - Change in the specification parameters

and/or limits of the finished product - Other variation

B.II.e.1.b.2 - Change in immediate packaging of the

finished product - Change in type/addition of a new

container - Sterile medicinal products and

biological/immunological medicinal products

B.II.e.1.b.3 - Change in immediate packaging of the

finished product - Change in type/addition of a new

container - Deletion of an immediate packaging

container without a complete deletion of a strength

or pharmaceutical form

B.II.f.1.d - Stability of FP - Change in storage

conditions of the finished product or the

diluted/reconstituted product








16/01/2020 18/02/2021 Annex II

Nimenrix

EMA/176236/2021 Page 9/39

































Nimenrix

EMA/176236/2021 Page 10/39





of the AS






B.I.b.1.z - Change in the specification parameters


material/intermediate/reagent - Other variation

B.I.b.2.a - Change in test procedure for AS or



IB/0097/G This was an application for a group of variations.

B.II.b.3.a - Change in the manufacturing process of

the finished or intermediate product - Minor change

in the manufacturing process




17/12/2019 n/a

PSUSA/10044

/201904




protein)

31/10/2019 n/a PRAC Recommendation - maintenance

Nimenrix

EMA/176236/2021 Page 11/39


B.II.b.3.c - Change in the manufacturing process of

the finished or intermediate product - The product is

a biological/immunological medicinal product and the

change requires an assessment of comparability

B.II.e.1.a.3 - Change in immediate packaging of the

finished product - Qualitative and quantitative

composition - Sterile medicinal products and

biological/immunological medicinal products

B.II.e.7.b - Change in supplier of packaging

components or devices (when mentioned in the

dossier) - Replacement or addition of a supplier

12/09/2019 n/a

IB/0093 C.I.z - Changes (Safety/Efficacy) of Human and


06/09/2019 n/a




of the AS



of the AS

02/07/2019 n/a

IA/0089 B.I.b.2.a - Change in test procedure for AS or



06/05/2019 n/a

II/0084 Update of section 4.2 of the SmPC in order to update

the posology information in infants, based on data

28/02/2019 04/10/2019 SmPC and PL The Nimenrix posology instructions were given for infants

(i) at 6-12 weeks of age and (ii) at >1yr old, thus leaving a

Nimenrix

EMA/176236/2021 Page 12/39

from study MenACWY-TT-087 (a phase IIIb,

controlled, randomised, open study aimed to

demonstrate the immunogenicity and safety of

Nimenrix in healthy infants) and MenACWY-TT-083

(an open-label, randomised and active controlled

study).

As a consequence, sections 4.4, 4.8 and 5.1 were

updated.

The MAH took the opportunity to include editorial

changes in sections 4.4 and 4.8 of the SmPC.



data

gap in advice for those between 12 weeks and 1 year of

age.

A post-hoc extrapolation exercise based on clinical studies

MenACWY-TT-087 and MenACWY-TT-083 was carried out

by the MAH. The data presented support (i) a 2+1 posology

for infants aged 6 weeks to 6 months and (ii) a 1+1

posology for infants from 6 to 12 months of age.

The posology instructions in SmPC section 4.2 have been

re-written in line with the accepted posology and presented

under new headings to emphasise ‘Primary immunisation’

vs ‘Booster doses’. Within each heading, the instructions

have been stratified by age group.

Sections 4.4, 4.8 and 5.1 have also been updated with the

appropriate information relating to the updated posology.

The PL has been updated accordingly.


B.II.b.1.c - Replacement or addition of a

manufacturing site for the FP - Site where any


release/control, and secondary packaging, for

biol/immunol medicinal products or pharmaceutical

forms manufactured by complex manufacturing

processes

B.II.b.2.b - Change to importer, batch release


Replacement/addition of a site where batch

24/01/2019 n/a

Nimenrix

EMA/176236/2021 Page 13/39

control/testing takes place for a biol/immunol

product and any of the test methods at the site is a

biol/immunol method

B.II.e.2.c - Change in the specification parameters

and/or limits of the immediate packaging of the

finished product - Deletion of a non-significant

specification parameter (e.g. deletion of an obsolete

parameter)

B.II.e.4.c - Change in shape or dimensions of the

container or closure (immediate packaging) - Sterile

medicinal products

B.II.e.4.c - Change in shape or dimensions of the

container or closure (immediate packaging) - Sterile

medicinal products

B.II.f.1.e - Stability of FP - Change to an approved

stability protocol

II/0083 Update of section 4.4 of the SmPC in order to include

a safety warning regarding the risk for invasive

disease caused by Meningococcal polysaccharide

serogroups A, C, W-135 and Y in persons with

familial complement deficiencies and persons

receiving treatments that inhibit terminal

complement activation.



data

13/12/2018 04/10/2019 SmPC Based on the review of the literature reports well as the

cases from the MAH’s safety database the Nimenrix SmPC

has been updated to reflect that persons with familial

complement deficiencies (for example, C5 or C3

deficiencies) and persons receiving treatments that inhibit

terminal complement activation (for example, eculizumab)

are at increased risk for invasive disease caused by

Neisseria meningitidis groups A, C, W-135 and Y, even if

they develop antibodies following vaccination with

Nimenrix.

IA/0088 A.4 - Administrative change - Change in the name

and/or address of a manufacturer or an ASMF holder

or supplier of the AS, starting material, reagent or

07/12/2018 n/a

Nimenrix

EMA/176236/2021 Page 14/39

intermediate used in the manufacture of the AS or

manufacturer of a novel excipient

PSUSA/10044

/201804




protein)


IA/0087/G This was an application for a group of variations.

B.I.a.4.b - Change to in-process tests or limits

applied during the manufacture of the AS - Addition

of a new in-process test and limits

B.I.a.4.c - Change to in-process tests or limits

applied during the manufacture of the AS - Deletion

of a non-significant in-process test




28/09/2018 n/a

IB/0085 B.II.b.3.a - Change in the manufacturing process of



17/09/2018 n/a

II/0082 B.II.f.1.c - Stability of FP - Change in storage

conditions for biological medicinal products, when the

stability studies have not been performed in

accordance with an approved stability protocol

13/09/2018 04/10/2019 SmPC

T/0080 Transfer of Marketing Authorisation

11/07/2018 30/07/2018 SmPC,

Labelling and

Nimenrix

EMA/176236/2021 Page 15/39

PL



manufacturing sites


manufacturing sites

17/07/2018 n/a

II/0078 C.I.11.b - Introduction of, or change(s) to, the

obligations and conditions of a marketing

authorisation, including the RMP - Implementation of

change(s) which require to be further substantiated

by new additional data to be submitted by the MAH

where significant assessment is required

12/07/2018 n/a

IB/0077 B.I.c.1.z - Change in immediate packaging of the AS

- Other variation

11/04/2018 n/a

IAIN/0076/G This was an application for a group of variations.

B.II.b.1.a - Replacement or addition of a

manufacturing site for the FP - Secondary packaging

site


stability protocol

26/03/2018 n/a

II/0074 Update of sections 4.5 of the SmPC to include new

information regarding co-administration of Nimenrix

with Boostrix and Cervarix in individuals from the

age of 9 to 25 years, based on data from Studies

MenACWY-TT-098 (116705- Phase 3 study to

15/03/2018 30/07/2018 SmPC and PL The MAH has updated the Product Information to include

new information regarding co-administration of Nimenrix

with a combined diphtheria (reduced antigen content),

tetanus and acellular pertussis vaccine and the human

papillomavirus vaccine [Types 16, 18] in individuals from

Nimenrix

EMA/176236/2021 Page 16/39

demonstrate the non-inferiority of Nimenrix co-

administered with Boostrix compared to Nimenrix

administered alone) and MenACWY-TT-054 (113823-

phase 3 study to demonstrate the non-inferiority of

Nimenrix co-administered with Cervarix compared to

Nimenrix alone). The Package Leaflet is updated

accordingly.

The MAH took also the opportunity to make editorial

revision to section 4.8 of the SmPC.



data

the age of 9 to 25 years.

The SmPC section 4.5 has been updated as follows:

[…]

In individuals aged 9 to 25 years, Nimenrix can be given

concomitantly with human papillomavirus bivalent [Type 16

and 18] vaccine, recombinant (HPV2).

[…]

One month after co-administration with a combined tetanus

toxoid, reduced diphtheria toxoid and acellular pertussis

vaccine, adsorbed (Tdap) in subjects aged 9 to 25 years,

lower GMCs were observed to each pertussis antigen

(pertussis toxoid [PT], filamentous haemagglutinin [FHA]

and pertactin [PRN]). More than 98% of subjects had anti-

PT, FHA or PRN concentrations above the assay cut-off

thresholds. The clinical relevance of these observations is

unknown. There was no impact of co-administration on

immune responses to Nimenrix or the tetanus or diphtheria

antigens included in Tdap.

The PL (section 2) has been updated accordingly.

Other medicines and Nimenrix

[…]

In individuals aged 9 to 25 years, Nimenrix can be given

concomitantly with human papillomavirus bivalent [Type 16

Nimenrix

EMA/176236/2021 Page 17/39

and 18] vaccine, recombinant (HPV2).

IB/0075 B.I.a.2.a - Changes in the manufacturing process of


of the AS

12/03/2018 n/a

II/0073 C.I.3.b - Change(s) in the SPC, Labelling or PL

intended to implement the outcome of a procedure

concerning PSUR or PASS or the outcome of the

assessment done under A 45/46 - Change(s) with

new additional data submitted by the MAH

22/02/2018 30/07/2018 SmPC

II/0069 B.I.a.1.e - Change in the manufacturer of AS or of a





25/01/2018 n/a

PSUSA/10044

/201704




protein)



B.II.e.2.b - Change in the specification parameters


finished product - Addition of a new specification

parameter to the specification with its corresponding

test method

B.II.e.2.b - Change in the specification parameters


19/10/2017 n/a

Nimenrix

EMA/176236/2021 Page 18/39

finished product - Addition of a new specification

parameter to the specification with its corresponding

test method

B.III.2.b - Change to comply with Ph. Eur. or with a




Member State





Member State





Member State


B.II.f.1.d - Stability of FP - Change in storage

conditions of the finished product or the

diluted/reconstituted product


stability protocol

B.II.f.1.z - Stability of FP - Change in the shelf-life or

storage conditions of the finished product - Other

variation

19/10/2017 n/a

IB/0067 B.II.d.2.a - Change in test procedure for the finished

product - Minor changes to an approved test

07/09/2017 n/a

Nimenrix

EMA/176236/2021 Page 19/39

procedure

N/0068 Minor change in labelling or package leaflet not

connected with the SPC (Art. 61.3 Notification)

17/08/2017 30/07/2018 Labelling

IB/0065 B.I.a.2.z - Changes in the manufacturing process of

the AS - Other variation

28/06/2017 n/a

PSUSA/10044

/201610




protein)


IA/0064 A.4 - Administrative change - Change in the name

and/or address of a manufacturer or an ASMF holder

or supplier of the AS, starting material, reagent or

intermediate used in the manufacture of the AS or

manufacturer of a novel excipient

26/04/2017 n/a

R/0059 Renewal of the marketing authorisation.

15/12/2016 16/02/2017 SmPC and PL Based on the review of data on quality, safety and efficacy,

the CHMP considered that the benefit-risk balance of

Nimenrix in the approved indication remains favourable and

therefore recommended the renewal of the marketing

authorisation with unlimited validity.

II/0062 B.I.d.1.a.3 - Stability of AS - Change in the re-test

period/storage period - Extension of storage period

of a biological/immunological AS not in accordance

with an approved stability protocol

09/02/2017 n/a

II/0049 Extension of Indication to include a wider paediatric

population starting from 6 weeks of age for

10/11/2016 12/12/2016 SmPC and PL Please refer to the published Assessment Report Nimenrix

H-2226-II-49-AR.

Nimenrix

EMA/176236/2021 Page 20/39

Nimenrix; as a consequence, sections 4.1, 4.2, 4.4,

4.5, 4.8 and 5.1 of the SmPC are updated. The

Package Leaflet and the RMP (version 6.0) are

updated in accordance.

C.I.6.a - Change(s) to therapeutic indication(s) -

Addition of a new therapeutic indication or

modification of an approved one

PSUSA/10044

/201604




protein)



B.II.b.1.a - Replacement or addition of a


site

B.II.b.2.c.1 - Change to importer, batch release


Replacement or addition of a manufacturer

responsible for importation and/or batch release -

Not including batch control/testing

22/09/2016 n/a

II/0058 Update of section 4.5 of the SmPC in order to add

new co-administration compatibility information with

Prevenar. Section 5.1 is proposed to be updated

following results of a new post hoc analyses

conducted to exclude 5 additional subjects from the

ATP cohort.

In addition, the Marketing authorisation holder

15/09/2016 12/12/2016 SmPC and PL

Nimenrix

EMA/176236/2021 Page 21/39

(MAH) took the opportunity to align the

pharmaceutical form of Nimenrix in Section 3 with its

product release specification following a complaint.

The Package Leaflet is updated accordingly.



data

IA/0060 B.I.a.4.a - Change to in-process tests or limits

applied during the manufacture of the AS -

Tightening of in-process limits

14/09/2016 n/a

II/0053 Update of sections 4.2, 4.8 and 5.1 of the SmPC to

reflect new booster and persistence data with a

follow-up of up to 5 years after vaccination with

MenACWY-TT. In addition, the MAH took the

opportunity to make minor editorial changes in the

SmPC, Labelling and Package Leaflet. An updated

RMP version 7.1 was agreed during the procedure.



data

21/07/2016 22/08/2016 SmPC,

Labelling and

PL

Nimenrix may be given as a booster dose in individuals who

have previously received primary vaccination with Nimenrix

or other conjugated or plain polysaccharide meningococcal

vaccines. In clinical trials, the use of Nimenrix as a booster

following primary vaccination with Nimenrix or other

meningococcal vaccines (quadrivalent meningococcal A, C,

W, and Y-DT conjugate vaccine or monovalent MenC

conjugate vaccines) was evaluated.

Nimenrix booster vaccination after priming in toddlers,

children, adolescents and adults: For subjects primed with

Nimenrix aged 1 year and above and boosted with

Nimenrix 4 or 5 years later, more than 99.0% of all

subjects achieved post-booster SBA titres 1:8 for both

assays (studies MenACWY-TT-062, 048, 059, 088). One

month after the booster vaccination, the GMTs elicited were

significantly higher than those elicited by age matched

naïve control groups, indicating that Nimenrix induces

immune memory to groups A, C, W-135, and Y.

The observed MenC booster response with Nimenrix was

Nimenrix

EMA/176236/2021 Page 22/39

similar to that observed in subjects primed and boosted

with a monovalent MenC-CRM conjugate vaccine. One year

after Nimenrix booster, SBA titres 1:8 persisted in at

least 95.5% of subjects (study MenACWY-TT-048, 12 to 23

months of age at primary vaccination).

When Nimenrix was used as a booster following primary

vaccination with a MenACWY-DT conjugate vaccine or a

monovalent MenC conjugate vaccine (study MenACWY-TT-

059, 10 to 25 years of age at primary vaccination and

study MenACWY-TT-088, 2 to 10 years of age at primary

vaccination), the titres increased by 48-340 fold for all

groups and 100% of the subjects reached SBA titres 1:8.

The local and general adverse reaction profile of a booster

dose of Nimenrix after primary vaccination with Nimenrix or

other conjugated or plain polysaccharide meningococcal

vaccines, was similar to the local and general adverse

reaction profile observed after primary vaccination with

Nimenrix, except gastrointestinal symptoms (including

diarrhoea, vomiting, and nausea) which were very

common.

II/0045 Update of sections 4.2, 4.4, 4.5, 4.8 and 5.1 of the

SmPC in order to amend the information related to

the vaccination phase of study MenACWY-TT-104

which includes immunogenicity results for the

meningococcal vaccine antigens, and reactogenicity

and safety up to one month after vaccination with

one or two MenACWY-TT doses in toddlers. This

change amends the condition related to study

MenACWY-TT-104. The variation leads to

amendments to the Summary of Product

Characteristics and Package Leaflet.

23/06/2016 29/07/2016 SmPC, Annex

II, Labelling

and PL

Update of sections 4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC

in order to amend the information related to the

vaccination phase of study MenACWY-TT-104 which

includes immunogenicity results for the meningococcal

vaccine antigens, and reactogenicity and safety up to one

month after vaccination with one or two MenACWY-TT

doses in toddlers. This variation amends the condition

related to study MenACWY-TT-104.

Nimenrix

EMA/176236/2021 Page 23/39

In addition the MAH is updating Annex II and IIIA in

accordance with the QRD template (v.9.1).

C.I.11.b - Introduction of, or change(s) to, the


authorisation, including the RMP - Implementation of

change(s) which require to be further substantiated

by new additional data to be submitted by the MAH

where significant assessment is required


B.I.a.1.k - Change in the manufacturer of AS or of a


















24/06/2016 n/a

Nimenrix

EMA/176236/2021 Page 24/39



manufacturing sites



of the AS



of the AS



of the AS



of the AS



of the AS



of the AS



of the AS



of the AS



of the AS


31/05/2016 n/a

Nimenrix

EMA/176236/2021 Page 25/39


of the AS



of the AS



of the AS



of the AS



of the AS



of the AS
















Nimenrix

EMA/176236/2021 Page 26/39

























PSUSA/10044

/201510




protein)


IB/0054 B.I.b.1.z - Change in the specification parameters


21/04/2016 n/a

Nimenrix

EMA/176236/2021 Page 27/39


IAIN/0052 B.II.b.2.c.1 - Change to importer, batch release


Replacement or addition of a manufacturer

responsible for importation and/or batch release -

Not including batch control/testing

15/01/2016 29/07/2016 Annex II and

PL

IAIN/0051 C.I.8.a - Introduction of or changes to a summary of

Pharmacovigilance system - Changes in QPPV

(including contact details) and/or changes in the

PSMF location

12/01/2016 n/a


C.I.11.z - Introduction of, or change(s) to, the


authorisation, including the RMP - Other variation







17/12/2015 n/a

T/0047 Transfer of Marketing Authorisation

13/11/2015 16/12/2015 SmPC,

Labelling and

PL

IA/0046 B.II.d.1.a - Change in the specification parameters

and/or limits of the finished product - Tightening of

specification limits

12/11/2015 n/a

Nimenrix

EMA/176236/2021 Page 28/39

PSUSA/10044

/201504




protein)



B.I.b.2.z - Change in test procedure for AS or


variation



variation



variation



variation

18/09/2015 n/a

WS/0748 This was an application for a variation following a

worksharing procedure according to Article 20 of

Commission Regulation (EC) No 1234/2008.



variation

30/07/2015 n/a



15/07/2015 n/a

Nimenrix

EMA/176236/2021 Page 29/39


















PSUSA/10044

/201410




protein)


II/0040 Update of section 5.1 of the SmPC based on the

results of a re-analysis that was performed excluding

immunogenicity data from subjects impacted by GCP

deviations for studies MenACWY-TT-036, MenACWY-

TT-043 and MenACWY-TT-038, and which included

antibody persistence Year 3- and Year 4- results

from study MenACWY-TT-043, and Year 4- results for

study MenACWY-TT-032. Further, the pooling of

clinical safety data in section 4.8 of the SmPC has

26/03/2015 28/07/2015 SmPC The information in section 5.1 of the SmPC for 3 of the

original Nimenrix studies has been updated as a

consequence of the reanalysis of data following issues

identified with GCP. The MAH has excluded data from

subjects who had not been properly consented, or where

serological data was missing. This includes 119 subjects

from MenACWY-TT-036 (out of a total of 1025 subjects),

106 subjects from MenACWY-TT-038 (out of a total of 1501

subjects), and 9 subjects from MenACWY-TT-043 (out of a

Nimenrix

EMA/176236/2021 Page 30/39

been updated, and section 4.2 of the SmPC has been

updated with removal of the sentence on the need

for a booster dose for increased clarity.



data

total of 689 subjects). The reason for the majority of

exclusions from MenACWY-TT-036 and MenACWY-TT-038

was consent issues, rather than missing serological data.

Furthermore, data from Years 3 and 4 in study MenACWY-

TT-036 show persistent immunogenicity in adolescents.

Persistence results from study MenACWY-TT-032 (Years 4

and 5 in toddlers) have also been updated to try to

minimise the potential of selection bias, since subjects with

rSBA MenC titres

Nimenrix

EMA/176236/2021 Page 31/39


material/intermediate/reagent - Widening of the

approved specs for starting mat./intermediates,

which may have a significant effect on the quality of

the AS and/or the FP

II/0037 To widen the approved specification limit of the

description test performed during quality control

release testing and stability testing of Nimenrix

conjugate bulks.

B.I.b.1.g - Change in the specification parameters


material/intermediate/reagent - Widening of the

approved specs for starting mat./intermediates,

which may have a significant effect on the quality of

the AS and/or the FP

26/02/2015 n/a






of the AS

26/02/2015 n/a

II/0033 B.II.b.1.c - Replacement or addition of a

manufacturing site for the FP - Site where any


release/control, and secondary packaging, for

biol/immunol medicinal products or pharmaceutical

forms manufactured by complex manufacturing

18/12/2014 n/a

Nimenrix

EMA/176236/2021 Page 32/39

processes

IG/0498 B.II.e.3.c - Change in test procedure for the

immediate packaging of the finished product -

Deletion of a test procedure if an alternative test

procedure is already authorised

21/11/2014 n/a




Change in test procedure for the finished product

B.II.d.2.z - Change in test procedure for the finished

product - Other variation

20/11/2014 n/a




minor change in the manufacturing process of the

active substance



of the AS

20/11/2014 n/a

PSUV/0027 Periodic Safety Update


IG/0468 B.II.e.2.c - Change in the specification parameters


finished product - Deletion of a non-significant

20/08/2014 n/a

Nimenrix

EMA/176236/2021 Page 33/39

specification parameter (e.g. deletion of an obsolete

parameter)

IB/0028 B.II.f.1.a.3 - Stability of FP - Reduction of the shelf

life of the finished product - After dilution or

reconstitution

20/08/2014 28/07/2015 SmPC,

Labelling and

PL























12/08/2014 n/a

Nimenrix

EMA/176236/2021 Page 34/39

IB/0025 B.I.a.4.z - Change to in-process tests or limits

applied during the manufacture of the AS - Other

variation

08/08/2014 n/a

PSUV/0020 Periodic Safety Update

22/05/2014 18/07/2014 SmPC and PL Refer to Scientific conclusions and grounds recommending

the variation to terms of the Marketing Authorisation(s)’ for

PSUV/0020.

IG/0446 C.I.8.a - Introduction of or changes to a summary of

Pharmacovigilance system - Changes in QPPV

(including contact details) and/or changes in the

PSMF location

24/06/2014 n/a

IB/0024 B.I.b.2.a - Change in test procedure for AS or



13/06/2014 n/a







25/04/2014 n/a

IA/0022 A.7 - Administrative change - Deletion of

manufacturing sites

18/04/2014 n/a

II/0009 Update of SmPC section 5.1 with long term data (up

to 4 years after primary vaccination) on antibody

persistence and booster response. The statements of

persistence of serum bactericidal antibody titres in

20/02/2014 23/04/2014 SmPC and

Annex II

Please refer to the assessment report: Nimenrix-H-C-2226-

II-09-AR

Nimenrix

EMA/176236/2021 Page 35/39

SmPC section 4.4 has been updated accordingly. In

addition, editorial changes have been made in SmPC

sections 4.2 and 5.1 and the Annex II has been

updated in line with latest QRD template version.

C.I.4 - Variations related to significant modifications

of the SPC due in particular to new quality, pre-

clinical, clinical or pharmacovigilance data

II/0016 Submission of results of a 5 year follow-up study of

the pivotal phase III study MenACWY-TT-039. The

study report was submitted in line with requirements

of Article 46 of Regulation (EC) No 1901/2006. The

requested variation proposed no amendments to the

PI.

C.I.13 - Other variations not specifically covered

elsewhere in this Annex which involve the submission

of studies to the competent authority

23/01/2014 n/a Please refer to the assessment report: Nimenrix-H-C-2226-

II-16-AR


C.I.12 - Inclusion or deletion of black symbol and

explanatory statements for medicinal products in the

list of medicinal products that are subject to

additional monitoring

A.z - Administrative change - Other variation

18/12/2013 n/a



17/12/2013 n/a

Nimenrix

EMA/176236/2021 Page 36/39



02/12/2013 n/a

IA/0015 B.I.b.1.b - Change in the specification parameters


material/intermediate/reagent - Tightening of

specification limits

25/10/2013 n/a

II/0014 Update of SmPC sections 5.1 and 4.8 with

immunogenicity and safety data in individuals above

55 years of age, based on results of a phase IIIb,

open label, randomised, controlled study. In SmPC

section 4.2 the statement on absence of data in

elderly population is being removed accordingly.

C.I.4 - Variations related to significant modifications

of the SPC due in particular to new quality, pre-

clinical, clinical or pharmacovigilance data

24/10/2013 23/04/2014 SmPC The MAH submitted results of a study, where single dose of

Nimenrix was administered to 194 Lebanese adults 56

years of age and older (including 133 aged 56-65 years and

61 aged > 65 years). The percentage of subjects with rSBA

titres (measured at MAH’s laboratories) ≥ 128 before

vaccination ranged from 45% (MenC) to 62% (MenY).

Overall, at one month post-vaccination the percentage of

vaccinees with rSBA titres ≥ 128 ranged from 93% (MenC)

to 97% (MenY). In the subgroup aged > 65 years the

percentage of vaccinees with rSBA titres ≥ 128 at one

month post-vaccination ranged from 90% (MenA) to 97%

(MenY). All adverse reactions reported in this study were

already observed in younger age groups.




B.II.b.3.b - Change in the manufacturing process of

the finished product - Substantial changes to a

manufacturing process that may have a significant

impact on the quality, safety and efficacy of the

medicinal product

24/10/2013 n/a

Nimenrix

EMA/176236/2021 Page 37/39




Changes on the manufacturing process of the active

substance.

B.I.a.2.c - Changes in the manufacturing process of

the AS - The change refers to a [-] substance in the

manufacture of a biological/immunological medicinal

product and is not related to a protocol

27/06/2013 n/a

IG/0306 C.I.z - Changes (Safety/Efficacy) of Human and


12/06/2013 n/a

IG/0304 A.4 - Administrative change - Change in the name

and/or address of a manufacturer or supplier of the

AS, starting material, reagent or intermediate used

in the manufacture of the AS

17/05/2013 23/04/2014 Annex II

IG/0297 C.I.z - Changes (Safety/Efficacy) of Human and


19/04/2013 n/a

II/0005 Change in the manufacturing process of the finished

product.

B.II.b.3.b - Change in the manufacturing process of

the finished product - Substantial changes to a

manufacturing process that may have a significant

impact on the quality, safety and efficacy of the

medicinal product

21/03/2013 n/a

Nimenrix

EMA/176236/2021 Page 38/39

IA/0007 B.II.d.2.a - Change in test procedure for the finished

product - Minor changes to an approved test

procedure

04/02/2013 n/a

IG/0265/G This was an application for a group of variations.

C.I.9.e - Changes to an existing pharmacovigilance

system as described in the DDPS - Changes in the

major contractual arrangements with other persons

or organisations involved in the fulfilment of

pharmacovigilance obligations and described in the

DD

C.I.9.h - Changes to an existing pharmacovigilance

system as described in the DDPS - Other change(s)

to the DDPS that does not impact on the operation of

the pharmacovigilance system

28/01/2013 n/a




Change of specifications of reagent.




17/01/2013 n/a


B.II.b.2.a - Change to batch release arrangements

and quality control testing of the FP - Replacement

or addition of a site where batch control/testing

05/10/2012 n/a

Nimenrix

EMA/176236/2021 Page 39/39

takes place

B.II.b.1.z - Replacement or addition of a

manufacturing site for the FP - Other variation

IAIN/0001 B.II.b.1.a - Replacement or addition of a


site

17/07/2012 n/a


C.I.9.c - Changes to an existing pharmacovigilance

system as described in the DDPS - Change of the

back-up procedure of the QPPV

C.I.9.h - Changes to an existing pharmacovigilance

system as described in the DDPS - Other change(s)

to the DDPS that does not impact on the operation of

the pharmacovigilance system

12/07/2012 n/a

Documents

Nimenrix, INN-meningococcal group A, C, W-135 and Y ...€¦ · Business Park, Clondalkin, Dublin 22, Ireland) as an 16/01/2020 SmPC, Labelling and PL ; Nimenrix EMA/CHMP/652267/2020